Measures of percent stenoses and current quantitative coronary arteriography fail to define severity of diffuse coronary artery disease (CAD) or multiple segmental stenoses since the "normal" reference segment is often narrowed and cumulative effects of multiple stenoses are not considered. Therefore, we developed the theoretical basis and methodology for quantitatively analyzing the entire epicardial arterial tree on arteriograms by accounting for cumulative effects of diffuse disease or multiple stenoses based on measured arterial lumen size compared to what the expected normal arterial size and/or arterial flow should be for the size of the dependent coronary vascular bed throughout the coronary tree determined regionally from the sum of arterial and branch lengths by validated techniques. Our extensive results from experimental animals and patients document basic physical principles underlying epicardial tree structure, our method, and that coronary artery lumen area in patients with CAD is diffusely 30% to 50% smaller than normals for the regional mass of the distal myocardial bed. This project extends this anatomic analysis of the epicardial arterial system to the more physiologic measure of disease severity, regional coronary flow reserve, throughout the coronary arterial tree derived from its anatomic lumen size-branch length relations on coronary arteriograms, thereby linking the anatomic and functional characteristic of the entire coronary vascular tree affected by diffuse and multi segmental disease. The specific aims are to test in a multistenosis animal model and in man the hypotheses (1) For diffuse CAD or multiple stenoses, regional coronary flow reserve predicted from our extended quantitative method equals total and regional coronary flow reserve directly measured by radiomicrospheres, electromagnetic flow meter and/or intracoronary Doppler (2) The complex cumulative effects of multiple stenoses or diffuse disease in a cascade of branching arteries alters regional coronary flow reserve in ways that cannot be measured or estimated from the single worst stenosis and produce complex, unexpected fluid dynamic interactions including (a) coronary "branch steal" in the absence of collaterals caused by non stenotic arterial branches arising between serial stenoses of the parent artery (b) improved coronary flow reserve after PTCA in one stenotic branch associated with worsening coronary flow reserve in another stenotic branch in parallel due to "branch steal" caused by unbalanced stenoses in a cascade of branching arteries (c) in three vessel CAD, successful PTCA often fails to restore coronary flow reserve to normal due to diffuse disease or multiple stenoses (d) a small improvement in lumen diameter, e.g. 70% to 60% diameter stenosis diffusely by risk factor modification causes much greater improvement in coronary flow reserve than PTCA of proximal 70% stenoses which leaves diffuse or multiple stenoses distally.